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Use offructus schisandrae sphenantherae and its extract for multidrug resistance for treating tumour

A technology of schisandra extract and multidrug resistance, which is applied in the field of schisandra and schisandra extract as a multidrug resistance reversal agent, which can solve the problems of unsatisfactory drug resistance reversal effect, toxic side effects, and cardiovascular toxicity in solid tumors

Inactive Publication Date: 2006-08-09
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, many compounds have been found to have strong tumor multidrug resistance reversal effects in vitro and in vivo animal experiments, such as calcium channel blockers including verapamil, calmodulin antagonists, cyclosporins, Quinolines and anti-estrogens, however, when used clinically, in addition to the relatively certain reversal effect on some blood system tumor drug resistance, the reversal effect on solid tumor drug resistance is not ideal
It is generally believed that these compounds cannot achieve an effective reversal concentration in the body at a dose that can be tolerated by the human body, and once the dose is increased to make the blood drug concentration reach the concentration with reversal activity in the in vitro test, serious toxic and side effects will occur. Or when reversal agents are used in combination with antineoplastic drugs, the pharmacokinetic parameters of antineoplastic drugs will be changed, resulting in unforeseen toxic and side effects
For example, verapamil as a positive control in the present invention has strong tumor resistance reversing activity in vitro, but it is found that cardiovascular toxicity is produced when it does not reach the concentration of reversing drug resistance when applied to the body, thus limiting its clinical use

Method used

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  • Use offructus schisandrae sphenantherae and its extract for multidrug resistance for treating tumour
  • Use offructus schisandrae sphenantherae and its extract for multidrug resistance for treating tumour
  • Use offructus schisandrae sphenantherae and its extract for multidrug resistance for treating tumour

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Take KB, KBv200, MCF-7, MCF-7 / Adr, Bel in the logarithmic growth phase 7402 The cells were seeded in a 96-well culture plate (Coster), and after 24 hours of culture, gradient concentrations of anticancer drugs, reversal agents and control solvents were added. Continue to cultivate for 72 hours, then discard the culture medium, add 0.5 mg / ml thiazolium (MTT) 100 μl (diluted with RPMI 1640 culture medium without serum) to each well, continue to cultivate for 4 hours, discard the thiazolium, add to each well 150 μl of dimethyl sulfoxide was shaken slightly to dissolve the precipitate, and the absorbance was measured at 570 nm in a microplate reader (Bio-Rad 450 type). Set up three to four replicate wells in each group and take the average value to calculate the IC 50 . 10 μmol / L verapamil was used as a positive control. See Table 1-10 for specific results.

[0045] drug

[0046] drug

[0047] drug

[0048] drug

[0049] ...

Embodiment 2

[0056] Take the logarithmic growth period Bel 7402 Cells, when the cells cover 70-80% of the bottom of the bottle, replace the RPMI 1640 culture medium containing 10 μmol / L doxorubicin, and add Schisandra chinensis extract with a final concentration of 25 μg / ml, with 10 μmol / L verapamil as Positive control, three parallel samples for each group, 37°C, 5% CO 2 Continue to incubate for 3 hours, collect the cells after washing three times with ice-cold PBS (pH 7.4), take a certain number of cells, suspend the cells with 1.2ml hydrochloric acid (0.3N)-ethanol (50%), and break the cells on a sonicator Afterwards, centrifuge at 10,000rpm for 15 minutes, take 1.0ml of the supernatant and add 2.0ml of the above-mentioned hydrochloric acid-ethanol solution, measure the fluorescence value of adriamycin with a fluorescence spectrophotometer, the excitation wavelength is 470nm, and the emission wavelength is 580nm. Content-fluorescence standard curve calculation 10 6 Amount of doxorubic...

Embodiment 3

[0058] Select Kunming mice with ascites type S180 sarcoma and H22 liver cancer in good growth state, pull the neck to kill, after the abdominal skin is disinfected with iodine wine and alcohol, the ascites is aspirated under aseptic conditions, and injected into a sterile Erlenmeyer flask (ice bath). Add normal saline to dilute to the appropriate concentration. Kunming mice were sterilized with iodine and alcohol on the right forelimb skin, subcutaneously inoculated in the armpit with 0.2ml of tumor fluid / mouse, and then administered in groups of 8-10 in each group on the next day. After 10 days, they were sacrificed, and the tumors were stripped and weighed. The administration method is as follows: for S180 sarcoma, Schisandra extract, 200 and 400 mg / Kg, for H22 liver cancer, Schisandra extract, 400 and 600 mg / Kg, orally, once a day, 10 times in total, oral volume: 10ml / Kg, solvent control , Tween 80, orally, once a day, 10 times in total, oral volume: 10ml / Kg; positive contr...

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Abstract

The present invention relates to a new application of Chinese medicinal material schisandra berry and its extract as multidrug drug-resisting reversion agent, in particular, it can be matched with anti-tumor drug for curing tumor with multidrug drug-resistance, and can raise the sensitivity of tumor cell to anti-cancer drug and can raise the effect for resisting tumor.

Description

technical field [0001] The invention relates to the new application of schisandra and schisandra extract as a multidrug resistance reversal agent, especially the new application of combining with antineoplastic drugs to treat multidrug resistant tumors and improving the sensitivity of tumor cells to anticancer drugs. The invention also relates to the new anti-tumor application of Schisandra chinensis. Background technique [0002] The acquired drug resistance of tumor cells after chemotherapy and the inherent drug resistance of some tumor cells are still one of the important reasons for the failure of tumor chemotherapy. The mechanism of multidrug resistance is very complicated. The main mechanism is the overexpression of multidrug resistance glycoprotein (P-gp) on the tumor cell membrane. Many chemotherapy drugs are substrates of P-gp, such as vinblastine , anthracyclines, epipodophyllotoxins, taxanes, etc. Reversing the multidrug resistance of tumor cells so as to restor...

Claims

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Application Information

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IPC IPC(8): A61K36/57A61K9/00A61P35/00A61K131/00
Inventor 刘耕陶黄敏金晶魏怀玲孙华
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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